Our case series has several important findings. Despite manufacturer and Food and Drug Administration (FDA) of not recommending sugammadex use in severe renal impairment, we found that it was being clinically utilized amongst pediatric anesthesia providers. Notably, there were no instances of deferred extubation, unplanned ICU admission, or need for supplemental oxygen after tracheal extubation, even in a patient with pre-existing noninvasive ventilation need who received a reduced dose of sugammadex. One patient required noninvasive ventilation on POD2 after undergoing a living donor renal transplant. Several findings provide validity that the increased respiratory requirement was primarily due to hypervolemia after multiple fluid rounds of fluid administration. Another had bronchospasm during emergence from anesthesia in the setting of upper respiratory symptoms and testing positive for rhinovirus/enterovirus. The event was quickly and effectively treated with no sequalae. Isolated bronchospasm during emergence from anesthesia is not an uncommon occurrence in pediatric patients and this patient was predisposed to increased airway reactivity and perioperative respiratory complications given the active infection. The absence of several clinical signs and therapies typically found in cases of anaphylaxis makes this an unlikely explanation for the bronchospasm. Thus, based on detailed review of the clinical circumstances surrounding each of these events, we concluded that no adverse events identified were definitively attributable to the administration of sugammadex in pediatric patients with stage IV or V CKD. It should be noted, however, that without quantitative neuromonitoring demonstrating complete recovery of TOF, the possibility of residual neuromuscular weakness cannot be ruled out, even if not clinically present.

Sugammadex and the sugammadex-NMBA complex are renally excreted unchanged. Currently, the FDA does not recommend the use of sugammadex in end stage kidney disease due to prolonged plasma half-life and possible dissociation of sugammadex-NMBA complex in the setting of decreased renal clearance, resulting in free rocuronium that may recurarize. Our study builds upon prior pharmacokinetic studies demonstrating no clinical evidence of residual weakness or recurrence of neuromuscular blockade in end-stage renal patients [7, 8, 12, 13]. The sugammadex-NMBA complex could dissociate theoretically, however, the likelihood may be low given the high association constant (Ka 107 M−1) and stability of the complex’s chemical composition [14]. Even when dissociation occurs, rapid re-association may occur due to the strong binding affinity of these molecules, which may make it difficult to identify recurrent neuromuscular blockade, if it occurs at all.

Residual neuromuscular blockade may remain in up to 5% of patients receiving sugammadex [15, 16]. Interestingly, the rocuronium-sugammadex complex was detectable in plasma at day 7 after administration in 6 renally impaired patients in a study by Panhuizen et al., furthering the concern that there remains prolonged exposure of the rocuronium-sugammadex complex in this population [13]. The potential effects of this in the neonatal population requires special attention. Neonates have a large volume of distribution with an extracellular fluid compartment comprising up to 80–90% of the whole body. Elimination can be longer in neonates and recovery from neuromuscular blockade slower, especially if multiple doses are administered. This, combined with an immature neuromuscular junction and lower plasma concentration required to produce paralysis, necessitates careful and patient-specific consideration of risk and benefit when utilizing sugammadex in these populations. Sugammadex administration in this population is not yet approved and further highlights the need for appropriate monitoring of depth of neuromuscular blockade for accurate dosing of NMBA antagonism.

There are multiple limitations in this study. The use of sugammadex in patients with CKD stage IV and V is considered “off-label” and not recommended by the manufacturer and FDA. Since the introduction of sugammadex into our formulary in November 2016, it has been widely utilized [17]. The single center nature of this study is another limitation, including data collection from a single center, small sample size, and risk of non-detection when using ICD coding for identification of subjects [18]. Importantly, recurarization could not definitively be identified due to a lack of quantitative neuromonitoring at our institution. Without the use of quantitative monitoring, the role of sugammadex and residual neuromuscular blockade cannot be dismissed, even if not clinically evident. Given the retrospective review, factors such as type of neuromonitoring device, type of muscle monitored, and presence of fade were not controlled, which challenges the accuracy of sugammadex dosing. Variability in documentation of TOF, timing of drug administration, and other intraoperative events is an inherent limitation of this study. Additionally, no comparisons could be made to be to an age and gender matched historical cohort because of the small sample size. This was a case series designed to describe a range of safety outcomes in pediatric patiens with CKD stage IV and V receiving sugammadex; including a matched cohort would have altered the study design. Although our findings suggest that sugammadex may have a role for neuromuscular reversal in patients with pediatric severe renal impairment, further studies are warranted to elucidate its safety and efficacy in pediatric patients, including the neonatal population who is especially vulnerable given its unique pharmacokinetics.